The aim of this project is to investigate biological substrates of schizophrenia by integrating regional electrophysiologic measures with available data from other neuroimaging studies on the same subject. Cortical and subcortical abnormalities associated with dimensions of schizophrenic symptomatology will be identified by comparing EEG and evoked potential (EP) parameters to neuroanatomic and neurophysiologic data. First, the association between electrophysiologic measures of regional brain activity and indices of regional cerebral blood flow (CBF) and metabolic rates (CMR) will be examined by recording EEG and CMR simultaneously during resting states and recording EEG, probe EPs and CBF during activation states. Staged analyses of these data will identify which indices are sensitive to activation and subsequent cross modality analyses will assess the concurrent validity of the measures. Second, specific patterns of electrophysiologic abnormalities and associated neuroanatomic (magnetic resonance imaging, MRI) and neurophysiologic (CBF and CMR) measures will be related to schizophrenic symptomatology. To test the hypothesis that negative symptoms in schizophrenics are associated with cortical atrophy and decreased cortical activity, presence and topography of EEG slow activity will be correlated with cerebral spinal fluid (CSF) volume in brain and these will be related to presence of negative symptoms using logistic regression. To determine whether positive symptoms in schizophrenics are associated with a primary dysfunction in subcortical structures and secondary abnormalities in cortical processing characterized by overactivation of left hemisphere regions, these measures will be supplemented by EP experiments. Two EP components with hypothesized subcortical contributions, the auditory P1 and the P300, will be examined. Again, staged analyses will be used to determine both presence and regional specificity of abnormalities. identified abnormalities will then be related to presence and severity of positive symptoms using regression models. Subcortical contributions of EP components will be assessed by correlating P1 and P300 abnormalities with the presence of CMP abnormalities in the thalamus and limbin structures, respectively. To determine whether EEG, probe EPs, and CBF measures indicate overactivation of left hemisphere regions in schizophrenics with positive symptoms, regional abnormalities in those measures found to be sensitive to activation will be correlated with the presence and severity of positive symptoms.